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The use of circulating nucleic acids as diagnostic and/or prognostic tools in oncology has been widely documented. Likewise, in gynecology and obstetrics, the development of a non-invasive prenatal diagnostic tool, based on the study of these biomarkers, has confirmed their growing interest in this discipline. Apart from the oncological interest of these free DNA fragments, Assisted Reproduction has discovered an easily measurable molecular tool guiding the management of infertile couples. Several studies have focused on the microRNAs present in the ovarian follicle and their involvement in folliculogenesis. Regarding the assay of cell-free DNA in seminal plasma of men with sperm alterations, there are no solid data yet. The level of cell-free DNA varies depending on the pathophysiological context and reflects the proportion of apoptotic and/or necrotic events occurring in the body. Therefore, its blood test could provide additional help to practitioners in the assessment of ovarian functional status. The cell-free nucleic acids could constitute new biomarkers predictive of oocyte and/or embryonic quality and represent a promising avenue in the prevention of implantation failures.